Name: evaluating skilled prehension in mice using an auto-trainer
Uploaded: 2019-09-12T13:30:00
Description: Watch this Scientific Journal Video about Evaluating Skilled Prehension in Mice Using an Auto-Trainer at JoVE.com

自动训练装置由杰森·邓索恩、乌里·塔施和丹·塔施在步进分析有限责任公司建造，设计输入支持和由罗伯特·哈伯德、理查德·奥布赖恩和史蒂文·泽勒提供说明。
尚帕利莫未知中心的特雷莎·杜阿尔特提供了关于描述和分类小鼠到达行动的宝贵见解和想法。

此处描述的所有方法均已获得约翰霍普金斯大学ACUC（动物护理和使用委员会）的批准。
1. 准备鼠标笼子供使用
<ol><li>从每个保持架前端的底座创建宽度为 0.8 厘米和 7 厘米高度的开槽开口，如图1所示。这个槽作为动物到达的开口。 注：自动训练器专为大多数动物研究用品供应商提供的标准小鼠笼尺寸（如图1所示）而设计。此...

<ol>
	<li>Whishaw, I. Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+endpoint,+descriptive,+and+kinematic+comparison+of+skilled+reaching+in+mice+(mus+musculus)+with+rats+(rattus+norvegicus).">An endpoint, descriptive, and kinematic comparison of skilled reaching in mice (mus musculus) with rats (rattus norvegicus).</a> Behavior Brain Research. 78, 101-111 (1996).</li><li>Farr, T. D., Whishaw, I. Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantitative+and+qualitative+impairments+in+skilled+reaching+in+the+mouse+(mus+musculus)+after+a+focal+motor+cortex+stroke.">Quantitative and qualitative impairments in skilled reaching in the mouse (mus musculus) after a focal motor cortex stroke.</a> Stroke. 33, 1869-1875 (2002).</li><li>Zeiler, S. R., Krakauer, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+interaction+between+training+and+plasticity+in+the+poststroke+brain.">The interaction between training and plasticity in the poststroke brain.</a> Current Opinion in Neurology. 26, 609-616 (2013).</li><li>Klein, A., Sacrey, L. A., Whishaw, I. Q., Dunnett, S. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+use+of+rodent+skilled+reaching+as+a+translational+model+for+investigating+brain+damage+and+disease.">The use of rodent skilled reaching as a translational model for investigating brain damage and disease.</a> Neuroscience and Biobehavioral Reviews. 36, 1030-1042 (2012).</li><li>Zeiler, S. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Medial+premotor+cortex+shows+a+reduction+in+inhibitory+markers+and+mediates+recovery+in+a+mouse+model+of+focal+stroke.">Medial premotor cortex shows a reduction in inhibitory markers and mediates recovery in a mouse model of focal stroke.</a> Stroke. 44, 483-489 (2013).</li><li>Becker, A. M., Meyers, E., Sloan, A., Rennaker, R., Kilgard, M., Goldberg, M. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+automated+task+for+the+training+and+assessment+of+distal+forelimb+function+in+a+mouse+model+of+ischemic+stroke.">An automated task for the training and assessment of distal forelimb function in a mouse model of ischemic stroke.</a> Journal of Neuroscience Methods. 258, 16-23 (2016).</li><li>Bruinsma, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+automated+home-cage-based+5-choice+serial+reaction+time+task+for+rapid+assessment+of+attention+and+impulsivity+in+rats.">An automated home-cage-based 5-choice serial reaction time task for rapid assessment of attention and impulsivity in rats.</a> Psychopharmacology. , 1-12 (2019).</li><li>Francis, N. A., Kanold, P. O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Automated+operant+conditioning+in+the+mouse+home+cage.">Automated operant conditioning in the mouse home cage.</a> Frontiers in Neural Circuits. 11 (10), (2017).</li><li>Balcombe, J. P., Barnard, N. D., Sandusky, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Laboratory+routines+cause+animal+stress.">Laboratory routines cause animal stress.</a> Contemporary Topics in Laboratory Animal Science. 43, 42-51 (2004).</li><li>Fenrich, K. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improved+single+pellet+grasping+using+automated+ad+libitum+full-time+training+robot.">Improved single pellet grasping using automated ad libitum full-time training robot.</a> Behavior Brain Research. 281, 137-148 (2015).</li><li>Ng, K. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fluoxetine+maintains+a+state+of+heightened+responsiveness+to+motor+training+early+after+stroke+in+a+mouse+model.">Fluoxetine maintains a state of heightened responsiveness to motor training early after stroke in a mouse model.</a> Stroke. 46 (10), 2951-2960 (2015).</li><li>Whishaw, I. Q., Suchowersky, O., Davis, L., Sarna, J., Metz, G. A., Pellis, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impairment+of+pronation,+supination,+and+body+co-ordination+in+reach-to-grasp+tasks+in+human+parkinson's+disease+(pd)+reveals+homology+to+deficits+in+animal+models.">Impairment of pronation, supination, and body co-ordination in reach-to-grasp tasks in human parkinson's disease (pd) reveals homology to deficits in animal models.</a> Behavior Brain Research. 133, 165-176 (2002).</li><li>Dobrossy, M. D., Dunnett, S. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+influence+of+environment+and+experience+on+neural+grafts.">The influence of environment and experience on neural grafts.</a> Nature Review Neuroscience. 2, 871-879 (2001).</li><li>Alaverdashvili, M., Foroud, A., Lim, D. H., Whishaw, I. Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=&amp;#34;Learned+baduse&amp;#34;+limits+recovery+of+skilled+reaching+for+food+after+forelimb+motor+cortex+stroke+in+rats:+A+new+analysis+of+the+effect+of+gestures+on+success.">&amp;#34;Learned baduse&amp;#34; limits recovery of skilled reaching for food after forelimb motor cortex stroke in rats: A new analysis of the effect of gestures on success.</a> Behavior Brain Research. 188, 281-290 (2008).</li></ol>

我们的自动培训师以自动的方式评估前肢的伸向（前肢）。为了实现这一端点，许多专为小鼠捕集任务设计的参数，包括颗粒放置、颗粒大小和训练标准，已迭代数年，并根据以前的协议2、5进行修改，6.这里的进步是使用机器人实现任务的自动化，该机器人允许家庭笼式外壳。家庭笼外壳使小鼠保持平静，以更少的焦虑执行?...

实验测试运动技能前神经损伤和后神经损伤以及调整运动训练的时间、数量和类型的方法对转化研究具有重要意义。在过去的十年里，由于遗传操作的易用性，小鼠已经成为一种流行的模型系统，可以阐明损伤前和损伤后的运动学习机制。然而，小鼠的行为检测没有像其他哺乳动物（尤其是大鼠）那样得到优化。此外，老鼠和老鼠的行为之间有重要的区别，这强烈地暗示了以不同方式训练这两个物种1，2。
熟练的前体运动使用手/爪将食物放入嘴里，操纵物体，或使用工具。事实上，伸手去掌握日常生活中的各种物体是上肢的基本功能，而伸手可吃的行为是许多哺乳动物使用的一种自我控制形式。许多遗传、生理和解剖学的变化，支持前恒技能的获取，已经在领域3中得到了很好的定义。在将临床前发现转化为临床结果时，需要一个高效且可重复的相关测试。对啮齿动物和人类接触的研究表明，在人类和动物中，习性行为是相似的。因此，这些相似性表明，前体测试可以作为研究运动学习以及人类疾病损伤和治疗的翻译模型。因此，评价小鼠的发病可以为研究健康和疾病状态的转化研究提供强有力的工具。
不幸的是，老鼠的先验任务，即使是小规模的实验室设置，可能既费时又费时。为了缓解这个问题，我们在这里描述一个自动版本的预处理任务。所述任务要求小鼠通过小鼠的家笼正面槽伸出一只爪子，将延长的爪子拉上，抓住食物颗粒奖励，并将颗粒拉回笼子内部食用。所得数据以成功或失败的形式呈现。这种自动化成功地记录了数据，并减轻了研究人员必须承担任务的负担和时间。

<table border="0" cellpadding="0" cellspacing="0" style="width:1319px;" width="1318">
	<tbody>
		<tr height="19">
			<td height="19" style="height:19px;width:318px;">ABS Filament</td>
			<td style="width:242px;">Custom 3D Printed</td>
			<td style="width:166px;">N/A</td>
			<td style="width:595px;">utilized for pellet holder, frame, arm and funnel</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">ABS Sheet</td>
			<td>McMaster-Carr</td>
			<td>8586K581</td>
			<td>3/8&#34; thickness; used for platform compononents, positioning stand guides and base</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Adruino Mini</td>
			<td>Adruino</td>
			<td>A000087</td>
			<td>nano version also compatiable as well as other similar microcontrollers</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Bench-Top Adjustable-Height Positioning Stand</td>
			<td>McMaster-Carr</td>
			<td>9967T43</td>
			<td>35 lbs. load capacity</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Clear Acrylic Round Tube</td>
			<td>McMaster-Carr</td>
			<td>8532K14</td>
			<td>ID 3/8&#34;</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Low-Carbon&#160;Steel Wire</td>
			<td>McMaster-Carr</td>
			<td>8855K14</td>
			<td>0.148&#34;&#160;diameter</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Pellet Dispenser</td>
			<td>Lafayette Instrument: Neuroscience</td>
			<td>80209-45</td>
			<td>with 45 mg interchangeable pellet size wheel and optional stand</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Photointerrupter Breakout Board&#160;</td>
			<td>SparkFun</td>
			<td>BOB-09322 ROHS</td>
			<td>designed for Sharp GP1A57HRJ00F</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Reflective Object Sensor</td>
			<td>Fairchild Semiconductor</td>
			<td>QRD1113</td>
			<td>phototransistor output</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Servo Motor</td>
			<td>SparkFun</td>
			<td>S8213</td>
			<td>generic metal gear (micro size)</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Transmissive Photointerrupter</td>
			<td>Sharp</td>
			<td>GP1A57HRJ00F</td>
			<td>gap: 10 mm, slit: 1.8 mm</td>
		</tr>
	</tbody>
</table>

evaluating skilled prehension in mice using an auto-trainer

我们描述了一种将天真的老鼠引入一种新颖的自命不及（达到把握）任务的方法。老鼠单独安置在笼子里，有一个正面槽，允许老鼠伸出笼子，取回食物颗粒。最小食物限制用于鼓励小鼠从槽中取回食物。当老鼠开始联想到槽里吃食物时，颗粒被手动拉开，以刺激爪子的延伸和刺激，通过正面槽抓住和取回颗粒。当小鼠到达槽时开始接触颗粒时，行为测定可以通过测量它们成功抓住并检索所需颗粒的速率来执行。然后，它们被介绍给一个自动训练器，自动为鼠标提供食物颗粒的过程，并记录成功和失败的到达和把握尝试。这允许以最小的工作量为多个小鼠收集到达数据，并酌情用于实验分析。

通常，建议每个训练单元包含大约 20-30 个试用单元，这些试验可能由用户设置，由自动培训器自动运行，并每节和鼠标保存到单个日志文件中。每个试验可以连续运行，就在其他试验之后，暂停 2-5 s。在自动训练器上训练的老鼠在 10 次训练中表现出技能的提高。
为了将自动训练器的效用与手动训练（被认为是黄金标准）进行...

Watch this Scientific Journal Video about Evaluating Skilled Prehension in Mice Using an Auto-Trainer at JoVE.com

Evaluating Skilled Prehension in Mice Using an Auto-Trainer

评估培训对运动技能的影响的方法是一个有用的工具。不幸的是，大多数行为评估可能是劳动密集型和/或昂贵的。我们在这里描述了一种机器人方法，用于评估小鼠的自理（达到-抓握）技能。

使用自动训练器评估小鼠的熟练前向

We describe a method to introduce na&#239;ve mice to a novel prehension (reach-to-grasp) task. Mice are housed singly in cages with a frontal slot that ...

我们的技术可自动执行复杂的行为分析，可以节省时间，并充当许多不同类型的研究的跳板。以我们的技术，任务和奖励是一回事。执行模糊任务（可能不正确）与获得奖励之间没有脱节。动物模型为测试方法提供了机会，以增强神经损伤后的复苏。例如，在我的实验室中，我们测试了增加中风后恢复的方法，因为迫切需要开发创新的中风后康复新方法。除了中风，我们的自动训练器可能可用于研究运动学习受伤前，以及帕金森氏症，阿尔茨海默氏症，或创伤性脑损伤的模型。当鼠标达到目标重量时，在槽前的颗粒表面上放置 45 毫克颗粒，开始训练，并允许鼠标取回颗粒。当鼠标将打开的槽与喂食关联时，使用一对钳子将颗粒放在与鼠标以前检索的颗粒相同的位置。当小鼠开始咬球时，将颗粒拉近约半厘米，使颗粒无法到达口腔。当鼠标伸出爪子穿过槽时，通过允许鼠标吃小丸子来强化行为。虽然对实验没有帮助，但记录左爪还是右爪是首选。当鼠标将爪子与吃小丸子关联时，通过扣住颗粒以响应用嘴和舌头取回颗粒来进一步强化行为。小心阻止你的老鼠不用爪子成功获得颗粒，否则他们会学会难以忘记的坏习惯。将 45 毫克颗粒放置在离笼门外边缘不到一厘米的地方，使颗粒的左或右点与从笼门槽边缘直伸出的直线切线切线，从而最终确定所需的爪子影响行为。然后允许鼠标尝试取回颗粒，警惕地取出颗粒，并防止其消耗，如果鼠标应尝试检索一些其他方法，而不是爪子延伸。在开始训练课前，单击自动训练器的 LabVIEW 界面中的"运行"箭头，并记下带和没有颗粒的诱饵颗粒传感器读数。单击"停止"以停止测试运行，将诱饵颗粒传感器目标更改为这两个读数之间的值。将修改后的鼠标笼放在自动训练器上并粘贴笼门。然后像手动步骤一样将颗粒与槽的边缘对齐，并在 LabVIEW 界面中打开新的培训课程。输入记录有关培训课程的数据所需的信息，然后单击"鼠标 ID"字段以输入每个培训课程的文件名。单击"常规过程中分配的总颗粒"字段，以控制为单个实验分配的颗粒值。单击"在从潜水板上移除指示的颗粒后暂停"字段以设置五秒暂停，然后单击"暂停长度"字段，在从潜水板中去除颗粒的时间与分配新弹丸的时间之间设置暂停。设置自动训练器以手动记录颗粒在"距离"字段中放置距离，然后单击"文件夹包含日志"字段以选择文件位置以保存收集的数据。填写信息字段后，单击"运行"以开始培训课程。自动训练器将分配单个颗粒并跟踪它们是否从漏斗中掉落，直到分配了颗粒总数，并且最后一个颗粒已被鼠标取回或丢弃。此时程序将自动停止。如有必要，也可以通过单击"停止"按钮提前停止。设置软件后，将鼠标的 home 保持架放在基座上进行测试，然后单击"运行"，让鼠标调查插槽及其新的不熟悉环境。接受过自动训练器训练的老鼠学习了预谋任务，并表现出明显的运动技能。这种技能的增加类似于观察到的动物在不使用自动训练器的情况下进行手动训练。一定要让老鼠用爪子。如果你让他们认为你只是让他们有食物， 他们就不会达到你。损伤可以诱发到运动通路的任何部分，以确定病变对运动性能的影响，以及如何鼓励从该病变中恢复。

Research

JoVE Journal

Behavior

Nest Building as an Indicator of Health and Welfare in Laboratory Mice

The minimization and alleviation of  suffering has moral and scientific implications. In order to mitigate this  negative experience one must be able to ...

科研

行为学

The Modified Hole Board - Measuring Behavior, Cognition and Social Interaction in Mice and Rats

修改后的孔板 - 测量行为，认知和社会互动小鼠和大鼠

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure ...

A Protocol for Housing Mice in an Enriched Environment

在丰富环境的协议房屋小鼠

Environmental enrichment (EE) is a housing environment for mice that boosts mental and physical health compared to standard laboratory housing. Our recent ...

Quantifying Social Motivation in Mice Using Operant Conditioning

量化的社会动机小鼠使用操作条件反射

In this protocol, social motivation is measured in mice through a pair of operant conditioning paradigms. To conduct the experiments, two-chambered ...

Acquisition of a High-precision Skilled Forelimb Reaching Task in Rats

收购高精度熟练的前肢到达任务大鼠

Movements are the main measurable output of central nervous system function. Developing behavioral paradigms that allow detailed analysis of motor ...

Determining Ultrasonic Vocalization Preferences in Mice using a Two-choice Playback Test

采用双选择播放测试确定超声波发声首小鼠

Mice emit ultrasonic vocalizations (USVs) during a variety of conditions, such as pup isolation and adult social interactions. These USVs differ with age, ...

An Operant Intra-/Extra-dimensional Set-shift Task for Mice

一个操作性内/外维特班任务的小鼠

Alterations in executive control and cognitive flexibility, such as attentional set-shifting abilities, are core features of several neuropsychiatric ...

Measuring Delay Discounting in Humans Using an Adjusting Amount Task

测量延迟贴现在人类使用的调量任务

Delay discounting refers to a decline in the value of a reward when it is delayed relative to when it is immediately available. Delay discounting tasks ...

Reinstatement of Drug-seeking in Mice Using the Conditioned Place Preference Paradigm

用条件位置偏好范式恢复小鼠药物寻毒作用

The present protocol describes the Conditioned Place Preference (CPP) as a model of relapse in drug addiction. In this model, animals are first trained to ...

Systematic Assessment of Well-Being in Mice for Procedures Using General Anesthesia

全身麻醉下小鼠幸福度的系统评价

In keeping with the 3R Principle (Replacement, Reduction, Refinement) developed by Russel and Burch, scientific research should use alternatives to animal ...